The evolving health care system has placed many new barriers and burdens on physicians such that there appears to be slowly decreasing the numbers of clinical investigators; thereby creating a potential crisis. This crisis will have multiple impacts on society and the health care system. One answer to this crisis is to support young, active and successful clinical investigators in order to overcome some of the major barriers to patient-oriented research: time, resources, and mentoring. Dr. Mack T. Ruffin represents one of these successful physicians with 15 years of specialty training and a commitment to mentoring the next generations of clinical investigators. This application is in response to the Midcareer Investigator Award in Patient-Oriented Research (PA-98-053). The areas of activity of this project are Dr. Ruffin's research plan focused on cancer chemoprevention in cervical and colorectal cancer along with his plan for mentoring beginning clinical investigators. The specific aims of the research projects are: (Three projects already have external support. This grant will allow further work by Dr. Ruffin on these projects.): Cervical Application of Retinoids Evaluation (CARE) Project (1) To determine if topical all-transretinoic acid reduces the number of viral genome copies of HPV per cell and/or inhibits HPV E6/E7 gene expression among 160-180 women with CIN II or III. Carotenoid-Rich Diet Trial to Reverse CIN I and II (CAPRE Study) (1) To determine if a carotenoid-rich diet high in fruits and vegetables given in a randomized and controlled study will cause significant increase in the regression rate of CIN I and CIN II among 326 women. Curcumin as a Chemopreventive Agent (1) To define the human pharmacokinetics of curcumin administered orally in the "Cyclox" micronized formulation for use as a nutritional supplement. Three additional projects will be developed in direct support from this grant over the next five years: COX-2 Specific Inhibitor (Celecoxib) and Sporadic Colorectal Polyps (1) To determine whether celecoxib reduces the recurrence of human adenomatous colonic polyps. HPV Infection and Diet (1) To determine if a carotenoid-rich diet high in fruits and vegetables will significantly reduce the incidence of HPV infection among college women. Finally, the findings of CARE Project and CAPRE Study will be used to further study other potential chemopreventive agents for cervical cancer.